In Michael Crichton’s recent novel Prey, the plot revolves around out-of-control nanobots threatening the word. However, although the reality for the future of nanotechnology will hopefully be more about how science at the nanoscale can change society for the better, avoiding a Crichton-like scenario, or the fear of one at least, will depend greatly upon the regulatory authorities ensuring the safe use of nanotechnology.
Nanotechnology is likely to have a substantial impact on the medical devices market. It is already clear that it will be used in diagnostics, drug delivery and implants, for instance. However, along with the benefits promised by revolutionary advances in medical treatment, comes the challenge of ensuring consumer safety.
To begin with, there is a need to define what constitutes nanotechnology. Without a robust definition there can be no effective regulation of devices incorporating nanotechnology. At present this is an issue that the appropriate authorities are dealing with both in the US and Europe.
Subhas Malghan, deputy director at the Center for Devices and Radiological Health (CDRH), part of the US Food and Drug Administration (FDA), says: “The FDA has a nanotechnology taskforce and one of the things we are struggling with is to define the phrase ‘nanotechnology’ at this stage, from the size perspective, we have accepted the definition of the National Nanotechnology Initiative [NNI], and we are working on the definition of 1–100nm.”
At the moment, however, the FDA is in the process of deciding what constitutes an acceptable definition. It expects to have its answer within the next couple of months.
Malghan adds: “At this stage, the manufacturing community can continue to adopt the NNI definition. That’s a safe thing to do until the FDA determines if there is going to be any difference in terms of our definition.”
THE GREAT UNKNOWN
Setting the definition issue to one side, there is, of course, the question of the science involved. Nanotechnology is an industry in its infancy.
Mark Morrison of the Institute of Nanotechnology at the University of Stirling in Scotland says: “It’s like talking about the Industrial Revolution, it covers so many different areas: it covers biosciences, material sciences and electronics, even construction, consumer goods health and cosmetics – a wide range of areas.
“This is real ‘frontier of science’ stuff and, unsurprisingly, when it comes to regulation, the big issues at the moment relate more to the science than the regulatory framework.
Malghan adds: “The basic challenge relating to regulation is that there are three specific areas that we have a lack of information about. The first is connected to the science of characterising nanoparticles, the second is concerned with the mechanistic understanding of the physical, chemical and biological interaction of these particles, and the third is related to the toxicity and behaviour of these nanoparticles in the in vivo environment.”
Morrison also points to the unknowns involved in the science: “In the case of engineered nanoparticles, some being used for drug delivery, treatment or imaging are small enough that they could potentially get into cells that you don’t want them to, and most people recognise that there needs to be more research done on this.
“If you consider a technical application in diagnostics, such as quantum dots, some of the materials involved, such as cadmium and germanium selenide, can be very toxic for cells, so there is a lot of investigation into encapsulating them.”
TOWARDS GREATER KNOWLEDGE
At the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), Steve Owen, head of European and regulatory affairs, highlights where further scientific investigation is likely to be directed in terms of understanding the science and quantifying the risks:
“Of the particular issues that may arise as a result of nanotechnology, there are two obviously significant areas. One is environmental: is there a risk of nanoparticles getting free into the atmosphere, into the environment, and if so does that matter – what happens if they do? The science on that is new and indecisive.”
“A second issue is that you can have a substance which, in a non-nano state, reacts in a certain way but when existing at the nano level, because of its size, may react in a different way.”
The FDA is certainly taking steps to address these issues: the CDRH, for example, has initiated interdisciplinary research programmes in the nanotechnology area over the last two years. In Europe, a working group has been established under the European Commission to look at medical devices and nanotechnology. It is examining not just the regulatory aspects, but also trying to identify particular issues that arise from dealing with nanoparticles.
REGULATING MEDICAL DEVICES
Beyond the scientific challenges, in terms of improving knowledge about nanotechnology and the need for standardised testing procedures, the regulatory framework appears to be sufficient to deal with medical devices incorporating nanotechnology.
Malghan says: “There are really no regulations as such, for nanotech-based devices. We are operating on the assumption that the current regulations are sufficient to regulate nanotechnology as we know it today.
“I would like to emphasise that we really have no plans to come up with any new regulations for nanotech-based devices at present.”
In the current risk-based regulatory process, of the three classes of product that are regulated, Malghan believes that most products will fall within classes two and three. And, while it is possible that complex devices could challenge existing regulations in the future, the CDRH has been monitoring the results of a major research programme at the National Cancer Institute in the US, which promises to produce many new drugs and devices and combination devices, and it is confident that the existing regulations are adequate to deal with what is currently in the pipeline.
It is a similar picture in the EU, explains Owen: “We have had a preliminary look at the issues of medical devices incorporating nanotechnology or nanoparticles, with a view to seeing whether the existing regulations are robust or not. Our conclusion, which the US has also reached, is that they probably are.”
IMPLICATIONS FOR MANUFACTURERS
As with other medical devices, manufacturers not only have to design and build their devices to incorporate all the essential regulatory requirements, but they also need to be able to demonstrate that they met those requirements.
Malghan says: “The focus should go back to understanding the science of the nanotechnology involved. Manufacturers need to really focus on the test procedures that they are going to use for characterising the materials and products, and what kind of test procedures they will use to evaluate the toxicity of these materials.
“The only caveat here is that we need more communication than we might do normally. The manufacturers need to disclose, as early as possible, that this is the technology that they are dealing with, what test procedures they are working with and what issues they are facing so we are all working with the same information.”
Malghan also points out that it might not always be easy to determine whether a medical product involves nanotechnology. This is not simply a question of definition.
He explains: “Nano-sized particles, as we understand them today, are very reactive. For example, if we analyse nano-sized particles in their own in vitro environment, the size distribution may be in the 1–100nm range. However, when they are put into actual use – to coat a polymeric film, for example – at that stage there is no assurance that the original nano particles will remain nano-sized.”
The only certainty seems to be that the science of nanotechnology is both new and complex. The next few years will undoubtedly see numerous new medical devices in development featuring nanotechnology.
For the present, however, the relevant regulatory bodies are confident that their regulatory frameworks are robust enough to deal with the technology. And, while manufacturers continue to work towards acceptable standardised testing procedures to demonstrate device safety, the world need not worry about a Crichton-like storyline being played out in real life.